B12, SAM, Folates Flashcards
When do you not want to give methotrexate?
Pregnancy
How does methotrexate work?
It is a folic acid inhibitor because it inhibits dihydrofolate reductase which is involved in the synthesis of tetrahydrofolate (THF). Without THF, synthesis of thymidine and purines cannot be synthesized, hindering DNA/RNA synthesis.
What is megaloblastic anemia?
The presence of many large and dysfunctional red blood cells in the marrow, resulting from an inhibition of DNA synthesis during red blood cell formation. This can result from a deficiency in B12/Folic Acid or from chemo therapy agents such as MTX.
What is tetrahydrofolate (THF)?
THF is the active form of folic acid, a carrier of one carbon units in the body, and is important in the formation of purines, thymine, and methionine. It is formed from folic acid by the enzyme dihydrofolate reductase.
What is the function of Vitamin B12?
Vitamin B12 functions in two important reactions.
- homocysteine to methionine This reaction is important because it also converts N5-methyl-THF back into THF. A failure in this reaction results in a folate deficency.
- L-methylmalonyl-CoA -> Succinyl CoA. A failure in this reaction results in demyelination (nerve damage).
What is intrinsic factor?
Intrinsic factor is a protein that is produced in the stomach that aids in the absorption of Vit. B12 in the small intestine. Without intrinsic factor, the body cannot absorb oral Vit B12, resulting in a deficiency.
What are the consequences of B12 deficiency?
Vitamin B12 deficiency results in:
- Secondary THF deficiency (anemia).
- Irreversible nerve damage due to demyelination.
- It results in problems with the methyl cycle (elevated blood homocysteine levels).
What are the consequences of THF deficiency?
- Megaloblastic anemia
- Elevated blood homocysteine
- Neural tube defects
What is the consequence of an intrinsic factor deficiency?
It results in reduced absorption of Vit B12 which can result in a secondary folic acid deficiency. Intrinsic factor deficiency is common in older people.
What is the methyl cycle?
The methyl cycle is a series of interconnected reactions that result in the formation of methyl group donors (such as SAM). This cycle is closely coupled with the formation of THF by Vit B12.
What is S-adenosyl methionine (SAM)?
A methyl group donor.
How are the methyl and folate cycles related?
The methyl cycle and folate cycle are connected by the homocysteine -> methionine reaction. Homocysteine accepts a methyl group from N5-methyl-THF, regenerating THF. This reaction is Vitamin B12 dependent.
